Mass spectrometry (MS) combined with on-line separations is a powerful tool for characterization of complex mixtures such as protein digests in proteomics studies. Separations instruments and methods include, but are not limited to, e.g., liquid chromatography (LC), gas chromatography (GC), capillary isoelectric focusing (CIEF), capillary zone electrophoresis (CZE), Capillary IsoTachoPhoresis (CITP), and ion mobility (e.g., IMS, FAIMS, or the like). FIG. 1 illustrates a contemporary process 100 for generating a mass accuracy histogram as will be known to those of skill in the mass spectrometry art. Spectra from, e.g., separation-FTICR MS measurements are compiled 105. Calibration coefficient values (A0, B0) obtained from an initial MS instrument calibration 110 are applied to spectra peak frequencies (f1, f2, . . . , fNm) obtained in the course of LC-MS measurements 115. Next, m/z values are calculated from the peak frequencies using FTICR MS instrument calibration function, e.g., m/z=A0/(f+B0) 120, from which a set of all observed m/z values (m/z1, m/z2, . . . , m/zNm) is compiled 125. Next, deisotoping provides a monoisotopic list of observed molecular masses (m1, m2, . . . , mNm) 130. A set of putative compounds (comp1, comp2, . . . , compNp) likely to exist in a sample is also compiled 135, from which a list of theoretical masses (mT1, mT2, . . . , mTNp) is calculated for each compound 140. A mass accuracy histogram is then generated by plotting the number of matches between the set of putative masses and the set of observed molecular masses as a function of the mass residual bin, i.e. the histogram of values (dm1, dm2, . . . , dmM), taken either in absolute units of the mass difference, or in the relative units of parts per million (ppm) 150. The mass accuracy histogram provides a measure of mass accuracy and mass precision that can be defined by the position of the histogram peak maximum and the peak width. Accurate mass measurements of complex mixtures can be compromised due to variability associated with mass spectra acquisition conditions over the course of an on-line separation, which is reflected in the mass accuracy histogram peak offset from 0 and having an increased width. Confident identification of thousands of compounds becomes feasible only if one obtains sufficiently high mass measurement accuracy. Accurate mass measurements require mass spectra acquisition conditions that include total ion current (TIC) or trapped ion population, and the distribution of ion abundances throughout the m/z range. Wide variations in these factors often occur, often beyond conditions providing the most accurate mass measurements. Accordingly, there remains a need for methods providing recalibration of mass measurement data from MS analyses that maximize mass accuracy and minimize mass errors permitting characterization of complex analyte mixtures.